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In a consanguineous family, exome sequencing identified two sisters with neurodevelopmental disorder harboring a novel homozygous PRPF8 c.257G>T (p.Arg86Met) variant, absent from population databases and predicted to be deleterious by protein modeling (PMID:40066647). The variant segregates in an autosomal recessive pattern in this single pedigree, with no reports of unrelated cases or extended familial segregation. Functional assessment was limited to in silico structural modeling indicating that p.Arg86Met may disrupt the Prp8 protein fold and spliceosomal interactions, without cellular or animal validation.
Current evidence supports a limited association between PRPF8 and MONDO:0700092 due to the small number of probands, absence of replication in unrelated families, and reliance on modeling data. Further independent case reports, segregation analyses, and experimental studies are required to establish causality and inform diagnostic decision-making. Key take-home: PRPF8 should be included in autosomal recessive neurodevelopmental disorder gene panels, but clinical utility remains provisional pending additional evidence.
Gene–Disease AssociationLimitedSingle consanguineous family; two probands; no extended segregation; modeling data only Genetic EvidenceLimitedTwo homozygous probands in one family; autosomal recessive inheritance; no additional segregation or replication Functional EvidenceLimitedProtein structural modeling indicates impact but lacks cellular or animal models |